DLG5

Chr 10AR

discs large MAGUK scaffold protein 5

Also known as: LP-DLG, P-DLG5, PDLG, YUVOB

NCBI Gene: 9231 ENSG00000151208 UniProt: Q8TDM6 OMIM: 604090

This gene encodes a scaffolding protein that regulates the Hippo signaling pathway, controls cell proliferation and epithelial polarity, and plays important roles in dendritic spine formation and synaptogenesis in cortical neurons. Mutations cause Yuksel-Vogel-Bauser syndrome, which follows autosomal recessive inheritance. The gene is highly constrained against loss-of-function mutations in the general population.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the family of discs large (DLG) homologs, a subset of the membrane-associated guanylate kinase (MAGUK) superfamily. The MAGUK proteins are composed of a catalytically inactive guanylate kinase domain, in addition to PDZ and SH3 domains, and are thought to function as scaffolding molecules at sites of cell-cell contact. The protein encoded by this gene localizes to the plasma membrane and cytoplasm, and interacts with components of adherens junctions and the cytoskeleton. It is proposed to function in the transmission of extracellular signals to the cytoskeleton and in the maintenance of epithelial cell structure. Alternative splice variants have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.261 OMIM phenotype

Clinical Summary— DLG5

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 265 VUS of 352 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.26LOEUF

pLI 0.999

Z-score 7.05

OE 0.17 (0.11–0.26)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.59Z-score

OE missense 0.79 (0.74–0.83)

919 obs / 1168.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.17 (0.11–0.26)

0≤0.351.4

Missense OE?0.79 (0.74–0.83)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 14 / 83.5Missense obs/exp: 919 / 1168.0Syn Z: -0.80

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedDLG5-related developmental disorderLOFAD

limitedDLG5-related developmental disorderLOFAR

This gene — mechanism propensity

0.3892th %ile

GOF

0.4184th %ile

LOF

0.74top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.26

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

352 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

VUS265

Likely Benign33

Benign16

Conflicting1

Pathogenic

265

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	0	0	0	3
Likely Pathogenic	0	0	0	0	0
VUS	1	261	3	0	265
Likely Benign	0	20	1	12	33
Benign	0	4	3	9	16
Conflicting	—				1
Total	4	285	7	21	318

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

9 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap DLG5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →